Henry joined SEIU as a researcher in 1980.[1][3][6] She had a natural gift for organizing, later saying, "I was always asked to get everybody organized to get on the bus and to get everyone to the dinner table on time."[4] Her experiences as a health care worker prompted her to work for a union that was involved in health care organizing.[5] She joined SEIU because it was one of the few unions hiring women as organizers at the time.[4]

In 1993, she was named director of the 475,000-member health care division of SEIU.[3][9]

Henry was elected to SEIU's Executive Board in December 1995 after President John Sweeney resigned after his election as President of the AFL-CIO.[10] SEIU President Andrew Stern named Henry his assistant for organizing in 1996.[1][6]

Henry was named assistant to then-SEIU Executive Vice President Eliseo Medina in 1998.[3] She remained active in the union's health care organizing, however, representing SEIU in its talks in 1999 to secure a card check agreement with the Catholic Healthcare West hospital chain.[3][11] More than 17,000 new members at 27 hospitals were organized under that agreement.[4] She was also involved in SEIU's successful negotiations with Tenet Healthcare for a card check agreement.[12]

She was named SEIU's Southern California organizing director in 2000,[3] the international union's chief healthcare strategist in 2004,[1] and elected an Executive Vice President of the union in 2004.[13][14] Henry helped oversee what she said in 2005 was a $150 million organizing budget, which SEIU intended to use to organize more than 1 million additional nurses over the next decade.[15][16] She helped negotiate a "no-raid agreement" [clarification needed] between SEIU and the United American Nurses in 2006.[3] In her first 25 years with SEIU, Henry played a major role in organizing drives at Beverly Enterprises, Catholic Health Care West, Tenet Healthcare, and HCA, Inc.[4][6] Stern relied on her to coordinate and lead important legislative efforts.[6] SEIU Executive Vice President Dennis Rivera took over Henry's healthcare organizing duties in early 2007.[17]

Henry and Medina helped plan the breakup of SEIU United Healthcare Workers West (UHW-West), a 140,000-member SEIU local, and force half its membership into a new statewide local which SEIU claimed would have enhanced collective bargaining and lobbying power.[18] UHW-West leaders balked at the plan, SEIU established a trusteeship over UHW-West, UHW-West leaders challenged the trusteeship and established an independent union (the National Union of Healthcare Workers, or NUHW), and the two unions began fighting over who would represent more than 100,000 employees in 350 bargaining units.[19][20][21] Henry expressed strong anger at the move to create an independent union.[20]

On April 13, 2010, several media sources reported that Stern would resign immediately as president of the union.[22][23][24] Stern resigned on Thursday, April 15. Anna Burger, SEIU's Secretary-Treasurer and the Chair of the Change to Win Federation, was named SEIU's interim president, to serve for 30 days until the SEIU Executive Board could name a permanent successor.[22] Burger was widely considered to be Stern's likely successor.[6][23][24][25] Henry was considered a dark horse candidate, although likely to challenge Burger for the presidency.[23][24][25] Several SEIU insiders urged Dennis Rivera to seek the presidency as well.[26] Stern, however, publicly endorsed Burger for the position.[6][27][28]

Support for Henry's candidacy swiftly grew. Within days of Stern's resignation announcement, four Executive Vice Presidents with the international union sent an e-mail announcing their support for her.[27][29] "Mary Kay's greatest strength is her ability to build consensus and create a highly effective team around shared goals and responsibilities. Mary Kay is the type of leader who motivates rather than demands", the note said.[6] The e-mail also cited the need "to return to organizing as our top priority" and "to restore our relationships with the rest of the union movement and our progressive allies."[30] Twelve days after Stern's announcement, national media reported more local unions representing more than 60 percent of SEIU's 1.9 million members had agreed to support Henry's candidacy.[6] Among the reasons why local union leaders backed Henry were the desire to have a fresh person in the leadership role, Henry was seen as a consensus builder, Burger was seen as too close to the authoritarian Stern, and Henry was viewed as more focused on organizing new members (while Burger was seen as focused on SEIU's political activity).[4][27]

National press reported that some local and regional SEIU leaders felt Henry would be less likely to continue Stern's local union merger program and more conciliatory to breakaway unions such as those in California.[21][30] But Burger's backers countered that Henry had never led a local union, had little on-the-ground organizing experience, and had associated with many SEIU staff and elected leaders tainted by recent scandals over financial impropriety.[27] Despite these charges, several large union locals in California and New York backed Henry.[28] Support for Henry also seemed to gain momentum when she told members of the international union's Executive Board that she favored letting local unions, not leaders based in Washington, D.C., set the union's agenda.[31] In a memo sent to SEIU leaders nationwide, Henry said, "Our local unions and divisions should drive our national priorities, not the other way around."[31] On April 28, Burger withdrew as a candidate for the presidency.[21][28][29] Burger said she would not resign as the union's Secretary-Treasurer, and endorsed Henry.[28][32]

Mary Kay Henry was elected President of SEIU by the international union's Executive Board on May 8, 2010, to serve the two remaining years of Stern's term. Her term as President will expire in 2012.[2] After her election, Henry said her major priorities as union president would be to advocate for labor rights, immigrants' rights, and LGBT rights.[4] However, she said she did not foresee bringing SEIU back into the AFL-CIO and refused to end the union's battles with its breakaway California locals.[4] A few days after her election, Henry began conducting a review of the duties and assignments of SEIU's top leadership and staff (including Secretary-Treasurer Burger), noting, "It is the prerogative of the president to reassign responsibilities."[33][34] Burger denied that she was thinking of quitting the union due to the review.[34]